Process for preparing azulenes



United States Patfiut 2,805,266 1 PROCESS on PREPARING AZULENES Karl Ziegler and Klaus Hafner, Mulheim an der Ruhr,

Germany No Drawing. Application March 6, 1956, V 7 Serial No. 569,695 j. Claims priority, application Germany March 7, 1955 -12 Claims. Cl. 260-666) wherein Z stands for hydrogen, Y represents a member of the group consisting of the halogens, the hydroxy-group, the alkoxy-groups and the substituted and unsubstituted amino-groups and the hydrogen atoms otherwise present in the molecule may be substituted by monovalent radicals and of the tautomers of'the said compounds to a temperature of about IUD-300 C.

- Preferably the azulene which is formed is removed as quickly as possible from the reaction chamber. In a preferred embodiment a cyclopentadiene, which is substituted in at least one orthoposition to the CH2 group by hydrogen, is condensed with a compound of the following general formula:

' substituted in at least once-position to the CHz-group and which may be substituted in the other positions is reacted with a quaternary pyridinium salt, and the intermediate products initially formed are converted into the corresponding azulenes either directly in a single process or after intermediate isolation.

.The course of the chemical reaction has still not been completely explained scientifically. Probably an N-alkyl- 1-cyclopentadienyl-dihydropyridine is initially formed as Well as the metal halide, and the former is then rearranged to form the corresponding fulvene with cleavage of the pyridine ring. For example, if sodium cyclopentadiene and pyridinium methylbromide are used as starting materials, there are initially formed sodium bromide and alkyl pyridinium halides, the salts of pyridine and'chloro- 2 probably the N-methyb1-cyclopentadienyl-dihydropyridine of the following formula 0 3 and then the latter is rearranged With-cleavage of the pyridine ring to form N-methyl-S-aminopentadiene-(2,4)--

yl-fulvene' of the following formula lac-03 H on p v H lHCH=CHOH=OHI ICHa .Cyclopentadienes -substituted in any desired manner can be used in place of unsubstituted cyclopentadiene as'the cyclopentadiene component, but in every case at least two. juxtaposed C-atoms must be unsubstituted and'no sub stituents should be present which disturb the systematic" course of the reaction. If it is desired 'to produce final products which contain a carboxylic acid group, it is'expedient to use starting'components which contain an esterifiedcarboxylic acid group and to split off the ester'group after completing the formation of the azulene. Examples of suitable substituents are amino, substitutedamino, alkyl, aryl and aralkyl groups. Indene is to be regarded as a substituted cyclopentadiene Within the scope of the present invention. It is just as suitable as a starting component as are its substitution products selected as above.

Suitable metal compounds of the cyclopentadienes are the alkali or alkaline-earth compounds. Provided that the operation is carried out in the presence of alkali metal alcoholates, it is also possible to use the free cyclopentadienes instead of the metal compounds of the cyclopentadienes.

Quaternary pyridinium compounds'substituted in any desired manner can be used as'pyridinium components, but also here it is necessary not to use any substituents which impede the course of the reaction. For example, 2,4-dinitrophenyl-N-pyridinium chloride, which can be prepared from 2,4-dinitrochlorobenzene and pyridine '(Th. Zincke,Liebigs Annalen, vol.- 333, ,1, 1904), can be con verted by heating with sodium cyclopentadiene in an inert high-boiling organic solvent, for example dibutyl ether, into the brownish coloured fulvene-like intermediate product, which yields azulen'e upon being heated with benzidine. Instead of sodium cyclopentadiene, monomeric cyclopentadiene can also be caused to act in the presence of alcoholic potassium on the pyridinium salt in order to obtain the same azulene-forming in'terine diate product; The reaction can also be conducted in liquid ammonia and proceeds particularly smoothly there'- i-n, since sodium cyclopentadiene is" soluble in liquid ammonia. Other quaternary salts of pyridine can be subjected to the reaction instead of the 2,4-dinitr0phenyl- N-pyridinium chloride, such as "quite generally the N- acetic acid, chloroformic acid esters, bromoacetone,

chloromethylether, chlorosulphonic 'acid or their esters, and also the N-4-pyridyl-pyridinium chloride hydrochlo- Patented Sept. 3, 1957 ride obtained from pyridine and thionyl chloride (Koenigs, Greiner, Ber. d. Deutschen Chemischen Gesellschaft, vol. 64, 1049, 1931), or pyridinium-glutaconic dialdehyde-diethylimide-diperchlorate (Schwarzen bach, Weber, Helv. Chim. Acta 25, 1628, 1942). These pyridinium salts, especially the N-alkyl or N-benzyl pyridin-ium halides, are prepared in a particularly simple manner. The salts, which are usually well crystallised, are obtained in a strongly exothermic reaction when the two components are mixed.

Since the component used for quaternising the pyridine compound is lost during the reaction, it is obvious for economic considerations that the cheapest possible components, such as benzyl chloride or methyl or ethyl chloride or bromide, should be used for this purpose. The same applies as regards the metal which is used for the formation of the cyclopentadiene-metal compound. It is also advisable here that for economic reasons the metals used should be the cheapest possible, such as sodium, potassium or calcium.

In one preferred form of the process according to the present invention, starting with a cyclopentadienefmetal compound and a quaternary pyridinium salt, the corre' sponding azulene is directly obtained in a single-stage process. The process can however also be carried out with isolation of the intermediate products. The inter mediate products primarily formed are probably of the type of 1-cyclopentadienyl-dihydropyridines and are very unstable, being transformed at room temperature into the. corresponding fulvenes with splitting off of the dihy dropyridine ring. Therefore, if it is desired to isolate the aforementioned intermediate products of the l-cyclo pentadienyl-dihydropyridine type, it is necessary to work under special conditions, for example low temperature and the use of liquid ammonia assolvent. The inter mediate products, probably of the fulvene type, are stable and can easily be isolated, so that the'process according to the invention can in each case also be carried out in two stages, with isolation of the fulvene intermediate products.

The present process makes it possible for the interme diate products described to be obtained quickly and simply and for the azulenes to be produced in relatively large amounts and in an economically advantageous manner from the said intermediate products.

Example 1 17.2 g. mol) of N-methyl pyridinium bromide areadded at -35 C. to a solution of 10.2 g. ($1 mol) of sodium methyl-cyclopentadiene in 200 cc. of liquid ammonia. The solution becomes yellowish red in colour and a yellow oil is precipitated. The ammonia is slowly evaporated and finally is filtered ofi in vacuo from the dark-red solid residue which is left. Theresidue is mixed with three times its weight of benzidine and this mixture is subjected in portions to distillation with steam superheated to 300 C. The distillate is again subjected 156 and its spectrum shows, inter alia, strong maxima at 738, 669 and 607 m/ Example 2 1.74 g. ,4 mol) of N-methyl-pyridinium bromide are finely triturated under nitrogen; with 0.9; g. of sodium cyclopentadiene and 50.0 g. of benzidine. Thismixture is heatedin a simple distillation apparatus at 250 C, and a gentle current of nitrogen isain'troduced'into the melt.

The bluev oil gives a trinitrobenzolate'with the melting point of.

The azulene formed is carried over by the nitrogen together with some benzidine, into a cooled receiver. When no further azulene passes over, the contents of the receiver are dissolved in acetone, the benzidine is converted with dilute hydrochloric acid into its water-soluble hydrochloride and the azulene is taken up in hexane. After drying the hexane phase, the hexane is distilled off in a small column. The crystalline azulene is left with a good yield.

Example 3 23.5 g. A mol) of a-methyl-pyridinium methyl bromide are well mixed with 9 g. of sodium cyclopentadiene and 150 g. of benzidine in a nitrogen atmosphere. This mixture is heated at 250-300" C. in a conventional distillation apparatus and a gentle stream of nitrogen is passed through the melt. A blue oil is distilled over, together with a small amount of benzidine. The reaction is completed after about 20 minutes. The contents of the receiver are taken up in hexane and the blue hexane solution is washed with dilute hydrochloric acid. This solution is then dried over calcium chloride and the hexane is distilled oil in a small column. A blue oil is left, which is shown to be 4-methyl-azulene. With trinitrobenzene, it yields a molecular compound with the melting point of 177-178 C. (from ethanol). The spectrum in the visible range shows strong maxima at 679, 618 and 567 III/p.

Example 4 dilute hydrochloric acid and the deep blue hexane layer is separated. The organic phase isv washed with water and dried over calcium chloride. The hexane is then distilledv off in a small column and a residue is obtained consisting of a blue oil, which is S-methyl azulene. Melting. point of the trinitrobenzolate: 147 C. (from ethanol). Absorption maxima: 616, 679, 648, 618, 591 m/u.

Example. 5

11.2 g. (55 mol) of -methyl pyridiniurn ethyl bro mide are added to a solution of 4.4 g. of sodium cyclopentadiene inliquid ammonia at 40 C. A yellowish red oil and sodium bromide are precipitated. The ammonia' is then evaporated and the residue is finally heated for ashort time at about 50 C. in vacuo for completely removing the ammonia. The residue is then thoroughly mixed with 50 g. of benzidine and this mixture is distilled with steam superheated to 300 C. A blue oil and benzidine are distilled over together with the steam. After the distillate has been worked up as described in Example 4, a bluish-violet crystalline compound is obtained, which is shown to be 6-methyl azulene on the basis of its melting point of 82-83 C. and also its trinitrobenzolate melting point of 140.S C. The spectrum of the 6-methyl. azulene obtained in this manner shows inter alia strong maxima at 681, 617 and 668 m/p.

Example 6 I is subjectedlto distillation with steam superheated to 300 C. A bluish-violet'oil distils over together with benzidine. The distillate is worked up as described in Example 4 and'finally a bluish-violet oil is obtained, which is 4,67 dimethyl azulene. It forms a trinitrobenzolate with the melting pointof 143 C. and its spectrum'in the visible range shows strong maxima at 660, 602 and550 m/ u.

Example 7 6.2 g. -mol) of 2,6-dimethyl pyridinium methyl bromide are finely triturated in a nitrogen atmosphere with 2.2 g. of sodium cyclopentadiene and 30 g. of benzidine and this mixture is heated under high vacuum at 300 C. A violet oil distils over together with the benzidine. After completion of the reaction, the contents of the receiver are dissolved in acetone. After adding 50 cc. of hexane, 100 cc. of water are added to the solution and thereafter such an amount of dilute hydrochloric acid that all the benzidine has entered into solution as hydrochloride. The organic phase is separated, washed neutral with dilute soda solution, dried over calcium chloride, and then the hexane is distilled off in a small column. As residue, there are obtained violet needles with the melting point of 69 C. this being 4,8-dimethyl azulene. The trinotrobenzolate melts at 178179 C. Absorption maxima: 662, 604, 673, 560 m/n.

Example 8 A mixture of 2.2 g. 5 mol) of quinolinium methyl bromide, 0.9 g. of sodium cyclopentadiene and 20 g. of benzidine are heated under high vacuum at about 300 C. A blue oil distils over together with the benzidine. The distillate is dissolved in acetone and, after adding hexane, the benzidine is washed out with dilute hydrochloric acid. After the blue hexane phase has been washed neutral, it is dried over calcium chloride and then the hexane is distilled ofi in a small column. The 4,5-benzazulene which is left forms with trinitrobenzene a molecular compound which has a melting point of 160-161 C What we claim is:

1. A method of producing azulenes, comprising the steps of reacting a pyridinium salt with a substance selected from the group consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group in the presence of a solvent so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so as to convert said in termediate reaction product to an azulene.

2. A method of producing azulenes, comprising the steps of reacting a pyridinium salt with a sodium compound of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group in the presence of a solvent so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100- 300 C. so as to convert said intermediate reaction product to an azulene.

3. A method of producing azulenes, comprising the steps of reacting a pyridinium salt with a potassium compound of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group in the presence of a solvent so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so as to convert said intermediate reaction product to an azulene.

4. A method of producing azulenes, comprising the steps of reacting a pyridinium salt with a calcium compound of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group in the presence of a solvent so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so as to convert said intermediate reaction product to an azulene.

5. A method of producing azulenes, comprising the steps of reacting a pyridinium salt selected from the group consisting of alkyl and aralkyl pyridinium salts with a which is substituted by hydrogen in at least one position adjacent to the CHz-group in the presence of a solvent so as to form an intermediate'reaction product; and subjecting the thus formed intermediate reaction product to a temperature of'about -300 C. so as to convert said intermediatere'action product to an azulene.

6.'A'method of producing azulenes, comprising the steps of reacting .a pyridinium salt with a' solution of ,a substance selected fromthegroup consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group dissolved in a solvent therefor so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction prod net to a temperature of about 100-300 C. so as to convert said intermediate reaction product to an azulene.

7. A method of producing azulenes, comprising the steps of reacting a pyridinium salt with a solution of a substance selected from the group consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group dissolved in liquid ammonia so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so as to convert said intermediate reaction product to an azulene.

8. A method of producing azulenes, comprising the steps of reacting a pyridinium salt selected from the group consisting of alkyl and aralkyl pyridinium salts with a solution of a substance selected from the group consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group dissolved in liquid ammonia so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so to convert said intermediate reaction product to an azulene.

9. A method of producing azulenes, comprising the steps of reacting a pyridinium salt selected from the group consisting of alkyl and aralkyl pyridinium salts with a solution of a substance selected from the group consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group dissolved in an organic solvent therefor under reflux conditions so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so as to convert said intermediate reaction product to an azulene.

10. A method of producing azulenes, comprising the steps of reacting a pyridinium salt selected from the group consisting of alkyl and aralkyl pyridinium salts with a solution of a substance selected from the group consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHa-group dissolved in liquid ammonia in the presence of a high boiling inert solvent of basic character so as to form an intermediate reaction product; and subjecting the thus formed intermediate reaction product to a temperature of about 100-300 C. so as to convert said intermediate reaction product to an azulene.

11. A method of producing azulenes, comprising the steps of reacting a pyridinium salt selected from the group consisting of alkyl and aralkyl pyridinium salts with a solution of a substance selected from the group consisting of alkali and alkaline earth metal compounds of a cyclopentadiene which is substituted by hydrogen in at least one position adjacent to the CHz-group dissolved in an organic solvent therefor under reflux conditions in the presence of a high boiling inert solvent of basic character so as to form an intermediate reaction product;

and: .subiectingv the thus formed intermedizite reaction high: Boiling inert solvent" of basic characterto a temproduct to a temperature of: about 100-300? C. soas perature}of'about1004300 C.

to convert said intermediate reaction product to' an 2 5 3; Ih d f d I I- I th References Cited in the file of this patent me: o '0 pro ucmg azu enes, comprising e 5 y w 7 I I step of heating a pyridinium salt selected from the group I I T E STATES PATENTS I I consisting of alkyl and aralkyl pyridinium salts and asub- 3 3 1 Zleglel 8t 00L 9, 1956 stance selected from the group consisting of alkali and I alkaline earth metal compounds of a cyclopentadiene I j OI'IHER I which is substituted by hydrogen in at least one posi- 10 Gordon: Chemical RWIEWS, 50, (Feb.

tion adjacent to the CHz-group in the presence of a PP- 

1. A METHOD OF PRODUCING AZULENES, COMPRISING THE STEPS OF REACTING A PYRIDINUM SALT WITH A SUBSTANCE SELECTED FROM THE GROUP CONSISTING OF ALKALI AND ALKALINE EARTH METAL COMPOUNDS OF A CYCLOPENTADIENE WHICH IS SUBSTITUTED BY HYDROGEN IN AT LEAST ONE POSISTION ADJACENT TO THE CH2-GROUP IN THE PRESENCE OF A SOLVENT SO AS TO FORM AN INTERMEDIATE REACTION PRODUCT; AND SUBJECTING THE THUS FORMED INTERMEDIATE REACTION PRODUCT TO A TEMPERATURE OF ABOUT 100-300*C. SO AS TO CONVERT SAID INTERMEDIATE REACTION PRODUCT TO AN AZULENE. 